Immune Checkpoint Inhibitor, Radiotherapy, Renal Cell Carcinoma
Conditions
Keywords
RCC, Multimodal radiotherapy
Brief summary
The objective of this single-center clinical study was to evaluate the disease control rate(DCR) and safety of multimodal radiotherapy in the treatment of patients with renal cell carcinoma (RCC) progressed after prior immunotherapy.
Detailed description
The patients who were clinically diagnosed advanced renal cell carcinoma with progression after 1-2 previous systemic therapies (at least one regimen containing immune checkpoint inhibitors, including combined VEGFR-TKI drugs), with two or more metastases at different sites, will be evaluated by the researchers. For eligible subjects, multimodal radiotherapy will be added to the treatment besides original immunotherapy or combinations of immunotherapy and TKIs after adjustment. The disease control rate and safety of this treatment will be evaluated.
Interventions
RADIATIONHigh-dose Radiotherapy (HDRT)
SBRT was adopted, and radiotherapy plan was made according to the location and size of lesions (total dose 20-70Gy, 5-12Gy every time).
RADIATIONLow-dose Radiotherapy (LDRT)
Radiotherapy plan was made according to the location and size of lesions (total dose 2Gy, 1Gy every time). After completing SBRT, LDRT was performed on as many metastatic sites as possible.
DRUGAnti-PD-1 monoclonal antibody
At the end of multimodal radiotherapy, immunotherapy was given within 7 days and in a subsequent LDRT. The maximum duration is 24 months.
Sponsors
Jinling Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Renal cell carcinoma confirmed histologically or cytopathologically, including unresectable or recurrent metastatic renal cell carcinoma. * Subject's previous treatment: Disease progression or intolerance following prior treatment with 1-2 systemic therapies (at least one regimen containing immune checkpoint inhibitors, including combined VEGFR-TKI drugs), And patients who have progressed within 12 months of prior immunoadjuvant or neoadjuvant therapy; According to the evaluation of attending physicians and professional radiotherapy doctors, it meets the standard of radiotherapy. * Patients can tolerate sequential immunotherapy while receiving radiation therapy. * At least two or more metastases at different sites are considered observable according to RECIST v1.1. * Subjects have fully understood and voluntarily signed an informed Consent form (ICF). * ECOG 0-1 points. * Major organs are functioning well. * Willing and able to comply with study plan visits, treatment laboratory tests, sample retention, and other procedures. * Fertile women must voluntarily use a highly effective contraceptive method (e.g., oral, injectable or implantable, barrier method, spermicide and condom, or intrauterine device) from the study period to ≥120 days after the last dose and have negative urine or serum pregnancy test results ≤7 days prior to enrolment. * Male patients who are not sterilized must voluntarily use highly effective contraception during the study period until ≥120 days after the last dose.
Exclusion criteria
* A history of malignancies other than the disease studied within the past 5 years, other than malignancies that are expected to be cured with treatment (including but not limited to adequately treated thyroid cancer, cervical carcinoma in situ, basal or squamous cell skin cancer, or breast ductal carcinoma in situ treated with radical surgery). * Systemic treatment with other antitumor agents, including targeted agents, immunotherapy agents and their combination regimens (eligible for inclusion after 5 half-lives), local antitumor therapy, or clinical investigational drug or device therapy, was administered 4 weeks prior to the first study. * Previous history of radiation therapy at any site or in any mode. * Had major surgery (as judged by the investigator) within 4 weeks prior to the first trial or was convalescing. * A history of severe drug allergy, including but not limited to antibody drugs. * Patients with contraindications to restart immunotherapy. * A known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation may require long-term adrenal corticosteroid therapy. * Patients with thyroid, suprarenal, or hypopituitarism that can be controlled with hormone replacement therapy alone, type 1 diabetes, and psoriasis or vitiligo that do not require systemic treatment are eligible to participate in this study. * Toxicity did not resolve after previous antitumor therapy, i.e. regression to baseline, prescribed grade 0 to 1 (except alopecia) as defined in NCI-CTCAE 5.0, or to the levels specified in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) | Up to 1 year | After completing the full course of radiotherapy, the patients underwent periodic imaging evaluation. Tumor imaging evaluations within 48 weeks should be performed every 6 weeks (±7 days) and every 12 weeks (±7 days) after 48 weeks until disease progression, loss of follow-up, death, withdrawal of study informed consent, subject initiation of other antitumor therapy, or study termination. DCR was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST v 1.1). |
| Incidence of adverse events | Up to 1 year | Adverse events according to Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). The patients must be on the trial for at least 8 weeks. Adverse events must be attributable to radiation therapy or immunotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | Up to 1 year | After completing the full course of radiotherapy, patients were followed for one year until the last visit or death. OS was measured based on data collected through professional procedures. |
| Progression-free survival (PFS) | Up to 1 year | After completing the full course of radiotherapy, the patients underwent periodic imaging evaluation. Tumor imaging evaluations within 48 weeks should be performed every 6 weeks (±7 days) and every 12 weeks (±7 days) after 48 weeks until disease progression, loss of follow-up, death, withdrawal of study informed consent, subject initiation of other antitumor therapy, or study termination. PFS was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST v 1.1). |
| Change of lymphocyte subsets and tumor-associated macrophages (TAMs) | 1 year | When making a radiotherapy plan, identify one or more LDRT lesions to be used for puncture. After the completion of the full course of radiotherapy, the predetermined lesions were punctured, and the obtained specimens were analyzed by pathological biopsy and immunohistochemistry to evaluate the changes of immune cells through the markers in tumor microenvironment. At the same time, the patient's blood was extracted and the numbers of relevant cells were detected. The changes of CD8+ T cells, CD4+ T cells, Treg, phenotype of TAMs and DCs were evaluated. |
| Abscopal effects | 1 year | When making a radiotherapy plan, identify one or more LDRT lesions to be used for puncture. After the completion of the full course of radiotherapy, the predetermined lesions were punctured, and the obtained specimens were analyzed by pathological biopsy and immunohistochemistry to evaluate the changes of tumor microenvironment. At the same time, the patient's blood was extracted and the relevant cytokines were detected for analysis. |
| Objective response rate (ORR) (partial response or complete response) | Up to 1 year | After completing the full course of radiotherapy, the patients underwent periodic imaging evaluation. Tumor imaging evaluations within 48 weeks should be performed every 6 weeks (±7 days) and every 12 weeks (±7 days) after 48 weeks until disease progression, loss of follow-up, death, withdrawal of study informed consent, subject initiation of other antitumor therapy, or study termination. ORR was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST v 1.1). |
Countries
China
Contacts
Primary ContactLe Qu, M. D.
Outcome results
None listed